A root avulsion injury physically separates spinal nerves from the spinal cord, leading to severe disruption of the root itself as well as the associated spinal cord segment. Avulsion injuries often occur in violent events, such as traffic and sports accidents or during a difficult childbirth. Following root avulsion, there is severe death of injured neurons, degeneration of axons, scar formation in the spinal cord and loss of synapses, which consequently result in disability of distal muscles and diminution of sensorimotor functions. The avulsed spinal nerve root is made up of a longer distal segment of peripheral nerve and a small fragment of central nervous tissue, which normally forms a dome that protrudes a short distance into the nerve. The interface between the central nervous system (CNS) and peripheral nervous system (PNS) is known as the transitional zone (TZ). The CNS part contains high numbers of astrocytes, which normally form channels within the basal lamina that allow the motor fibers to pass freely into the Schwann cell bands of Bungner. After avulsion injury, remaining astrocytes in the cord rearrange and hypertrophy to form a TZ scar similar to that which is found in a spinal cord injury. In order to restore motor function after avulsion, injured motoneurons must survive and regenerate axons, which need to elongate through inhibitory scar tissue in the TZ before re-entering into the peripheral nerve trunk and eventually form synapses with distal target muscles. Motoneuron survival and axonal regeneration can occur if the roots are surgically reimplanted, using proper techniques, onto the pia mater of the spinal cord close to the vicinity of the damaged ventral motoneuron pools. However, axon regeneration and functional recovery are still quite unsatisfactory. Reactive astrocytes synthesize and secrete inhibitory chondroitin sulfate proteoglycans (CSPGs) into the extracellular matrix, which create a growth impediment. Indeed, CSPGs have been known as the major inhibitor in scar tissue for years and digestion of lesion-induced CSPGs by Chondroitinase ABC (ChABC) enhanced axon regeneration and functional recovery after spinal cord injury.